For example, expression of PDE4B and PDE4D were both increased in the lungs by lipopolysaccharide (LPS), PDE4-inhibitors rolipram and roflumilast decreased mainly PDE4B [35], while roflumilast reversed the increased expression of PDE4B and PDE4D in the cerebral cortex and hippocampus of Alzheimer's Disease mice [36]. This evidence concerns the gene PDE4D and Alzheimer disease.